Non-Invasively Targeting, Probing, and Modulating a Deep Brain Circuit for Depression Alleviation

Area of Science:

• Neuroscience
• Psychiatry
• Medical Imaging

Background:

• Repetitive transcranial magnetic stimulation (rTMS) is a promising depression treatment.
• Focus has been on modulating the subgenual anterior cingulate cortex (sgACC).
• No prior studies linked sgACC TMS-evoked responses to clinical outcomes.

Purpose of the Study:

• To demonstrate sgACC circuit engagement using TMS-evoked responses.
• To investigate the relationship between sgACC TMS-evoked responses and clinical effects of rTMS for depression.
• To establish causal evidence of sgACC engagement and its clinical relevance.

Main Methods:

• Used interleaved single-pulse TMS/fMRI in 36 unmedicated depressed patients.
• Identified sgACC-connected cortical targets using rs-fMRI.
• Assessed TMS-evoked fMRI BOLD responses in sgACC before and after a 3-day iTBS rTMS intervention.

Main Results:

• Pre-intervention sgACC TMS-evoked response magnitude predicted depression improvement.
• More negative evoked responses correlated with greater clinical improvement.
• Post-intervention changes in evoked responses also associated with depression improvement, specific to the targeted pathway.

Conclusions:

• Demonstrated causal evidence of sgACC engagement via TMS/fMRI.
• Showed the clinical relevance of engaging and modulating the prefrontal-sgACC circuit.
• TMS-evoked responses in sgACC serve as a prognostic biomarker for rTMS treatment in depression.